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Glutamate and GABAA receptor crosstalk mediates homeostatic regulation of neuronal excitation in the mammalian brain

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4156-4173页

作者： Ya Wen Zhifang Dong Jun Liu peter axerio-cilies Yehong Du Junjie Li Long Chen Lu Zhang Lidong Liu Jie Lu Ning Zhou Dong Chuan Wu Yu Tian Wang DM Centre for Brain Health and Department of Medicine Vancouver Coastal Health Research InstituteUniversity of British ColumbiaVancouverBCV6T 2B5Canada Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing400014P.R.China iHuman Institue ShanghaiTech UniversityShanghaiP.R.China

Maintaining a proper balance between the glutamate receptor-mediated neuronal excitation and the A type of GABA receptor(GABAAR)mediated inhibition is essential for brain functioning;and its imbalance contributes to the pathogenesis of many brain disorders including neurodegenerative diseases and mental illnesses.Here we identify a novel glutamate-GABAAR interaction mediated by a direct glutamate binding of the GABAAR.In HEK293 cells overexpressing recombinant GABAARs,glutamate and its analog ligands,while producing no current on their own,potentiate GABA-evoked currents.This potentiation is mediated by a direct binding at a novel glutamate binding pocket located at theα+/β−subunit interface of the GABAAR.Moreover,the potentiation does not require the presence of aγsubunit,and in fact,the presence ofγsubunit significantly reduces the potency of the glutamate potentiation.In addition,the glutamate-mediated allosteric potentiation occurs on native GABAARs in rat neurons maintained in culture,as evidenced by the potentiation of GABAAR-mediated inhibitory postsynaptic currents and tonic currents.Most importantly,we found that genetic impairment of this glutamate potentiation in knock-in mice resulted in phenotypes of increased neuronal excitability,including decreased thresholds to noxious stimuli and increased seizure susceptibility.These results demonstrate a novel cross-talk between excitatory transmitter glutamate and inhibitory GABAAR.Such a rapid and short feedback loop between the two principal excitatory and inhibitory neurotransmission systems may play a critical homeostatic role in fine-tuning the excitation-inhibition balance(E/I balance),thereby maintaining neuronal excitability in the mammalian brain under both physiological and pathological conditions.

关键词： excitation thereby maintained

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Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： peter H.King Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SO

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

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Experimental investigation on slip conditions during thread rolling with flat dies

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Friction 2024年第1期12卷 136-143页

作者： Stefan VOLZ peter GROCHE Institute for Production Engineering and Forming Machines Technical University DarmstadtOtto-Berndt Straße 2Darmstadt 64287Germany

The process design of flat die rolling operations can be a tedious and costly process due to the challenges posed by small process windows.Within this work,an effort is made to closely investigate and understand the process limits caused by excessive slippage of the workpiece.Optical measurements are carried out to capture the characteristics of excessive slippage and the influence of the stroke rate and the tribological system on this process limit.Large differences in slippage were observed,depending on the tribological system.While systems with polymer based lubricants showed excessive slippage at low stroke rates,systems using oil or no lubricant endured higher stroke rates before process limits were reached.The optical measurements revealed three major forms of slippage:successful rolling without slippage,failure due to excessive slippage at process start,and failure due to excessive slippage at around one workpiece rotation.

关键词： rolling incremental forming thread rolling slippage profile rolling

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Diagnostic tools for fecal incontinence: Scoring systems are the crucial first step

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World Journal of Gastroenterology 2024年第6期30卷 516-522页

作者： peter Liptak Martin Duricek peter Banovcin Clinic of Internal Medicine-Gastroenterology University Hospital in MartinJessenius Faculty of Medicine in MartinComenius UniversityMartin 03601Slovakia

The main aim of this editorial is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023;29:4593-4603.This original research presents a new scoring system for fecal incontinence.Fecal incontinence is a chronic disease with a severe impact on the quality of life of the patients.Substantial social stigmatization often leads to significant underreporting of the condition even during visits to a specialist and could lead to further misman-agement or non-existent management of the disease.An important fact is that patients are often unable to describe their condition when not asked precisely defined questions.This problem is partially resolved by scoring questionnaires.Several scoring systems are commonly used;however,each of them has their shortcomings.For example,the absence of different kinds of leakage besides flatus and stool could further lead to underscoring the incontinence severity.Therefore,there has long been a call for a more precise scoring system.The correct identification of the presence and severity of fecal incontinence is paramount for further diagnostic approach and for choosing the appropriate therapy option.This editorial describes fecal incontinence,its effect on quality of life in general and further evaluates the diagnostic approach with a particular focus on symptom scoring systems and their implications for clinical practice.

关键词： Incontinence Fecal Scoring system Questionary Quality of life

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When to repair a retinal detachment?

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 607-609页

作者： peter Wiedemann Medical Faculty Leipzig UniversityLeipzig 04103Germany

Rhegmatogenous retinal detachment(RRD)is the most common retinal emergency,threatening visual acuity,with an incidence of 1/10000[1].The number of RRDs is increasing[2-3].I recently had to prepare two expert reports a... 详细信息

关键词： RRD visual reports

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A Population Dynamics Approach to the Distribution of Space Debris in Low Earth Orbit

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Communications on Applied Mathematics and Computation 2024年第1期6卷 340-353页

作者： John Jurkiewicz peter Hinow Department of Mathematical Sciences University of Wisconsin-MilwaukeeMilwaukeeWI53201USA

The presence of the debris in the Earth’s orbit poses a significant risk to human activity in outer space.This debris population continues to grow due to ground launches,the loss of external parts from space ships,and uncontrollable collisions between objects.A computationally feasible continuum model for the growth of the debris population and its spatial distribution is therefore critical.Here we propose a diffusion-collision model for the evolution of the debris density in the low-Earth orbit and its dependence on the ground-launch policy.We parametrize this model and test it against data from publicly available object catalogs to examine timescales for the uncontrolled growth.Finally,we consider sensible launch policies and cleanup strategies and how they reduce the future risk of collisions with active satellites or space ships.

关键词： Population dynamics Space debris Kessler syndrome Diffusion Low-Earth orbit

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A product version of the Hilton-Milner-Frankl theorem

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Science China Mathematics 2024年第2期67卷 455-474页

作者： peter Frankl Jian Wang Alfréd Rényi Institute of Mathematics Hungarian Academy of SciencesBudapest H-1053Hungary Department of Mathematics Taiyuan University of TechnologyTaiyuan 030024China

Two families F and G of k-subsets of {1, 2,..., n} are called non-trivial cross t-intersecting if|F ∩ G|≥t for all F ∈ F, G ∈ G and | ∩ {F : F ∈ F}| < t, | ∩ {G : G ∈ G}| < t. In the present paper,we determine the maximum product of the sizes of two non-trivial cross t-intersecting families of k-subsets of{1, 2,..., n} for n≥4(t + 2)2k2, k≥5, which is a product version of the Hilton-Milner-Frankl theorem.

关键词： extremal set theory cross t-intersecting family product version non-trivial

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Prefrontocortical Astrocytes Regulate Dominance Hierarchy in Male Mice

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Neuroscience Bulletin 2024年第3期40卷 415-417页

作者： Yong Tang Hai-Yan Yin peter Illes School of Acupuncture and Tuina Chengdu University of Traditional Chinese MedicineChengdu 610075China International Joint Research Center on Purinergic Signaling Chengdu University of Traditional Chinese MedicineChengdu 610075China Rudolf Boehm Institute for Pharmacology and Toxicology University of Leipzig04107 LeipzigGermany

Social hierarchy is a general self-organizational scheme in animal societies in which each member achieves a certain status of domination or subordination when getting access to resources,with profound consequences for survival,health,reproductive success,and multiple behaviors[1,2].The prefrontal cortex(PFC)was recognized as a central regulator of neuronal circuits determining the formation of social hierarchy;brain areas upstream of the PFC convey information about social status,and downstream brain regions execute dominance behavior[3].Social deficits have been suggested to be due to an elevation of excitatory/inhibitory(E/l)balance within the mouse dorsomedial(dm)PFC[4].A compensatory increase of inhibitory cell excitability partially rescued social deficits caused by such a disturbance of E/l balance.

关键词： consequences hierarchy determining

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Primary lateral sclerosis:more than just an upper motor neuron disease

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Neural Regeneration Research 2024年第9期19卷 1881-1882页

作者： Ee Ling Tan Jasmin Lope peter Bede Computational Neuroimaging Group(CNG) School of MedicineTrinity College DublinIreland Department of Neurology St James’s HospitalDublinIreland

Advances in clinical care and recent research achievements:Primary lateral sclerosis(PLS)has traditionally been regarded as a pure upper motor neuron condition,a view perpetuated by most medical textbooks.

关键词： sclerosis clinical traditionally

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Optimization of product characteristics of porous carbon agglomerates using a design of experiments in fluidized bed agglomeration

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Particuology 2024年第6期89卷 258-269页

作者： Martin Oelofse Robert Rack Marcelle Hilden peter Langguth Department of Pharmaceutical Technology and Biopharmaceutics Johannes Gutenberg UniversityMainzGermany Carbon Advanced Solutions GmbH HeuchelheimGermany

Spraying parameters during particle agglomeration processes can affect the agglomeration kinetics and particle growth.This study was conducted to better understand the influence of the spraying parameters in a fluidized bed wet agglomeration process,and the influence on the stability characteristics of carbon tablets.A formulation based on fine carbon and peroxide powder,as well as carboxymethyl cellulose as a binder,was used to produce agglomerates in a first production step.Thereafter in a second production step carbon tablets with a high porosity were molded for the customer goods industry.The optimization of the compressive strength of these carbon tablets was the goal of the trials.Carbon agglomerates were produced with a laboratory scale granulator called“ProCell”and were compressed with a five-cavity mechanical press.The screening of the agglomeration process parameters and their influence on the agglomerates quality,as well as the performance characteristics of the carbon tablets,were investigated using a multilevel factorial design.The experimental runs were done by varying atomized air pressure and feed rate of the fluid.This was determined by the design model.The findings of the statistical trials showed that low atomized air pressure and a low feed rate lead to a higher tablet compressive strength.

关键词： Wet agglomeration Fluidized bed Design of experiments Carbon agglomerates and tablets

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